US2016228570A1PendingUtilityA1
Novel Antibody And Use In Diagnosis And Therapy Of Arthropathies
Assignee: QUEEN MARY & WESTFIELD COLLEGEPriority: May 3, 2007Filed: Jan 4, 2016Published: Aug 11, 2016
Est. expiryMay 3, 2027(~0.8 yrs left)· nominal 20-yr term from priority
Inventors:Ahuva NissimYuti ChernajovskyBjarne FaurholmDavid PerrettPaul WinyardChristopher HughesStephen MatherFrancesco Dell'Accio
C07K 2317/76C07K 2317/565A61K 51/1096C07K 2317/569C07K 16/18C07K 2317/622C07K 2317/55A61K 47/6817A61K 47/6811A61K 47/6813A61P 19/02A61K 47/6849A61K 47/48415A61K 47/48538A61K 47/48423A61K 47/6843A61K 47/6851
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Claims
Abstract
The present invention provides a composition comprising an antibody or fragment thereof against oxidised Collagen II (CII) in which the antibody or fragment thereof is conjugated to a pharmaceutically active moiety. The invention also provides a composition comprising an antibody or fragment thereof against oxidised Collagen II (CII) and a detectable label. The invention further provides the use of such compositions in medicine, in particular for the treatment of an arthropathy, and in methods of diagnosis.
Claims
exact text as granted — not AI-modified1 . A composition comprising an antibody or fragment thereof against oxidised Collagen II (CII) in which the antibody or fragment thereof is conjugated to a pharmaceutically active moiety, wherein the antibody or fragment thereof comprises CDR sequences in the Variable Heavy (VH) chains and Variable Light (VL) chains as shown below, wherein the CDRH1 and CDRL1 sequences are the same as those of scFv 1-11E;
CDRH2
CDRH3
CDRL2
CDRL3
SISNSGTNTDYADSVKG
NYASFDY
YASYLQS
QQGSASPST
(SEQ ID NO: 7)
(SEQ ID NO: 45)
(SEQ ID NO: 65)
(SEQ ID NO: 92)
SIASSGTTTYYADSVKG
SYADFDY
AASNLQS
QQADTYPTT
(SEQ ID NO: 31)
(SEQ ID NO: 54)
(SEQ ID NO: 82)
(SEQ ID NO: 118)
SIDSAGDSTYYADSVKG
SYSYFDY
TASYLQS
QQASDYPTT
(SEQ ID NO: 35)
(SEQ ID NO: 58)
(SEQ ID NO: 85)
(SEQ ID NO: 122)
SIDTGGSYTDYADSVKG
SYTTFDY
SASYLQS
QQGSNSPTT
(SEQ ID NO: 37)
(SEQ ID NO: 59)
(SEQ ID NO: 75)
(SEQ ID NO: 124).
2 . A composition as claimed in claim 1 , in which the antibody is a polyclonal antibody or a monoclonal antibody.
3 . A composition as claimed in claim 1 , in which the antibody fragment is a Fc, Fab, scFv, single domain (dAb) antibody, diabody, minibody, or scFv-Fc fragment.
4 . (canceled)
5 . A composition as claimed in claim 1 , in which the antibody is an scFv selected from the group consisting of:
1-12A, 4-6A, 4-8A, 4-9F, 4-4H, 3-3A, 3-6F, 3-9D, 3-11E, 6-11D, 4-5H, 6-5F, and 6-7F.
6 . (canceled)
7 . A composition as claimed in claim 1 , in which the composition comprises a proteolytic cleavage site between the antibody or fragment thereof and the pharmaceutically active moiety.
8 . A composition as claimed in claim 7 , in which the proteolytic cleavage site is a matrix metalloproteinase (MMP) cleavage site, a serine protease cleavage site, or a site cleavable by a parasitic protease derived from a pathogenic organism.
9 . A composition as claimed in claim 8 , in which the proteolytic cleavage site is a MMP cleavage site.
10 . A composition as claimed in claim 9 , in which the MMP cleavage site is one or more of MMP1, MMP2, MMP3, MMP7, MMP8, MMP9 or MMP10 as shown in FIG. 5 .
11 . A composition as claimed in claim 1 , in which the pharmaceutically active moiety is an antibody or a fragment thereof, a growth factor, a differentiation factor, a cytokine molecule, an interferon, a bone morphogenetic protein (BMP);
a chemokine, a MCP (Monocyte Chemotactic Protein), a cytokine inhibitor; a cytokine receptor, a free-radical scavenging enzyme or a toxin, or an active fragment or portion thereof.
12 . A composition as claimed in claim 11 , in which the pharmaceutically active moiety is an interferon.
13 . A composition as claimed in claim 12 , in which the pharmaceutically active moiety is interferon beta (IFN-β).
14 . (canceled)
15 . A composition as claimed in claim 11 , in which the pharmaceutically active moiety is a TNF receptor (TNFR) antibody fusion protein.
16 . A composition as claimed in claim 15 , in which the pharmaceutically active moiety is TNFR2-Fc.
17 . (canceled)
18 . A composition as claimed in claim 1 , in which the pharmaceutically active moiety is a glycosaminoglycan molecule, chondroitin, a non-steroidal anti-inflammatory drug (NSAID), a steroid, sodium hyaluronate or hyaluronic acid, colchicine or hydroxychloroquine.
19 . A composition comprising an antibody or fragment thereof against oxidised Collagen II (CII) and a detectable label, wherein the antibody or fragment thereof comprises CDR sequences in the Variable Heavy (VH) chains and Variable Light (VL) chains as shown below, wherein the CDRH1 and CDRL1 sequences are the same as those of scFv 1-11E;
CDRH2
CDRH3
CDRL2
CDRL3
SISNSGTNTDYADSVKG
NYASFDY
YASYLQS
QQGSASPST
(SEQ ID NO: 7)
(SEQ ID NO: 45)
(SEQ ID NO: 65)
(SEQ ID NO: 92)
SIASSGTTTYYADSVKG
SYADFDY
AASNLQS
QQADTYPTT
(SEQ ID NO: 31)
(SEQ ID NO: 54)
(SEQ ID NO: 82)
(SEQ ID NO: 118)
SIDSAGDSTYYADSVKG
SYSYFDY
TASYLQS
QQASDYPTT
(SEQ ID NO: 35)
(SEQ ID NO: 58)
(SEQ ID NO: 85)
(SEQ ID NO: 122)
SIDTGGSYTDYADSVKG
SYTTFDY
SASYLQS
QQGSNSPTT
(SEQ ID NO: 37)
(SEQ ID NO: 59)
(SEQ ID NO: 75)
(SEQ ID NO: 124).
20 . A composition as claimed in claim 19 , in which the detectable label is a radionuclide or a dye.
21 . A composition as claimed in claim 20 , in which the detectable label is a dye.
22 - 23 . (canceled)
24 . A method of treatment of an arthropathy, comprising the step of administering to a subject a composition as claimed in claim 1 .
25 . (canceled)
26 . A method for the diagnosis of an arthropathy comprising the steps of administering a composition of claim 1 and subsequently detecting the composition.Cited by (0)
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